Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes
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Published on: October 4, 2019
Edith Yuan1, Kristie Liu1, Justin Lee2
1Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Abstract:
Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor, with an estimated annual incidence of 17 000 new cases in the United States. Current treatments for GBM include chemotherapy, surgical resection, radiation therapy, and antiangiogenic therapy. However, despite the various therapeutic options, the 5-year survival rate remains at a dismal 5%. Temozolomide (TMZ) is the first-line chemotherapy drug for GBM; however, poor TMZ response is one of the main contributors to the dismal prognosis. Long non-coding RNAs (lncRNAs) are nonprotein coding transcripts greater than 200 nucleotides that have been implicated to mediate various GBM pathologies, including chemoresistance. In this review, we aim to frame the TMZ response in GBM via exploration of the lncRNAs mediating three major mechanisms of TMZ resistance: (1) regulation of the DNA damage response, (2) maintenance of glioma stem cell identity, and (3) exploitation of hypoxia-associated responses.
Insights
Long non-coding RNAs (lncRNAs) drive glioblastoma (GBM) resistance to temozolomide (TMZ) chemotherapy. Understanding lncRNA roles in DNA repair, stem cell maintenance, and hypoxia is key to improving GBM treatment outcomes.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
- Current treatments offer limited survival benefits, with a 5-year survival rate of only 5%.
- Temozolomide (TMZ) resistance significantly contributes to treatment failure in GBM patients.
Purpose of the Study:
- To review the role of long non-coding RNAs (lncRNAs) in mediating TMZ resistance in GBM.
- To explore how lncRNAs influence DNA damage response, glioma stem cell identity, and hypoxia-associated pathways in GBM.
- To provide insights into potential therapeutic strategies targeting lncRNAs for overcoming TMZ resistance.
Main Methods:
- Literature review of studies investigating lncRNAs and TMZ resistance in GBM.
- Analysis of mechanisms including DNA damage repair, stem cell regulation, and hypoxia.
- Synthesis of current knowledge on lncRNA functions in GBM chemoresistance.
Main Results:
- lncRNAs are implicated in multiple mechanisms of TMZ resistance in GBM.
- Specific lncRNAs modulate DNA damage response pathways, affecting TMZ efficacy.
- lncRNAs play a crucial role in maintaining glioma stem cell characteristics and promoting survival under hypoxic conditions.
Conclusions:
- lncRNAs represent a significant factor in GBM's resistance to temozolomide chemotherapy.
- Targeting lncRNAs involved in DNA repair, stemness, and hypoxia offers a promising avenue for novel GBM therapies.
- Further research into lncRNA-mediated resistance mechanisms is essential for developing more effective glioblastoma treatments.
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